化疗栓塞方法和肝细胞癌组织反应

目的评价肝细胞癌肿瘤包膜、淋巴细胞浸润、纤维化、肝硬化等与经动脉化疗栓塞（TACE）方法的关系。方法观察117例手术切除的肝细胞癌肿瘤包膜、淋巴细胞浸润、纤维化、肝硬化程度,其中单纯手术58例,4种TACE后Ⅱ期手术切除59例。结果TACE组较单纯手术组,肝细胞癌包膜更厚、更完整,淋巴细胞浸润多,纤维化多（Ρ＜0.01）;包膜形成、纤维化与TACE方法、次数及手术间期密切相关（Ρ＜0.05）,淋巴细胞浸润与TACE方法、次数密切相关（Ρ＜0.05）,与手术间期关系不大（Ρ＞0.05）。肝硬化与治疗方法关系不大（Ρ＞0.05）,但与治疗次数相关（Ρ＜0.05）。结论多次、多材料联合栓塞TACE较单次、单材料栓塞、单纯化疗更易引起肝细胞癌包膜形成、淋巴细胞浸润、纤维化,超选择性插管可避免TACE对正常肝的损害。     

肝细胞癌经导管化疗栓塞治疗

肝细胞癌 (ｈｅｐａｔｏｃｅｌｌｕｌａｒｃａｒｃｉｎｏｍａ ,ＨＣＣ)多见于东亚、东南亚、东非、中非和南非。在我国发病率占恶性肿瘤的第二位。 1 985年统计 ,全国有 1 3 .8万新发病例 ,占世界总发病人数的 40 %～ 45 % [1 ] 。临床上有症状的ＨＣＣ患者未经治疗预后很差 ,中位生存时间仅为 1 .6个月。尽管目前对ＨＣＣ有诸多治疗方法 ,但总体疗效仍不能令人满意。外科手术仍然是改善预后的最主要手段 ,但仅适合 1 5 %～ 30 %的早期患者。 1 974年法国Ｄｏｙｏｎ等首先报道了用明胶海绵经导管肝动脉栓塞 (ｔｒａｎｓｃａｔｈｅｔｅｒａｒ…     

肝细胞癌动脉化疗栓塞术后并发脑梗死一例

肝细胞癌动脉栓塞治疗的并发症有很多,但栓塞术后并发脑梗塞的病例却十分罕见,我们在工作中遇到1例,现报道如下。     

经导管动脉化疗栓塞治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效观察

目的观察经导管动脉化疗栓塞(transcatheter arterial chemoembolization,TACE)治疗与联合索拉非尼治疗肝细胞癌合并门静脉癌栓的疗效。方法回顾性分析2010年7月—2013年11月东南大学附属中大医院江北院区收治的肝细胞癌合并门静脉癌栓患者107例,符合入组条件的40例中,21例接受TACE联合索拉非尼治疗（联合治疗组）,19例接受单纯TACE治疗（TACE组）,观察患者生存时间及严重并发症发生率。结果联合治疗组和TACE组的中位生存时间分别为8.4个月和5.7个月（P<0.001）,疾病无进展生存期分别为7.3个月和4.3个月（P=0.002）,2组严重并发症发生率分别为19.1%和15.8%（P=0.559）。结论TACE联合索拉非尼较单纯TACE治疗肝细胞癌合并门静脉癌栓未增加严重并发症发生率,并可有效延长患者生存时间。     

化疗栓塞后肝细胞癌细胞凋亡的研究

目的 研究肝细胞癌患者经动脉化疗栓塞（ｔｒａｎｓａｒｔｅｒｉａｌｃｈｅｍｏｃｅｍｂｏｌｉｚｔｉｏｎ,ＴＡＣＥ）治疗后肿瘤细胞凋亡的情况。方法 用光学显微镜（简称光谱）和流式细胞仪对１１７例手术切除的肝细胞癌标本进行凋亡检测;其中单纯手术５８例４种介入治疗后二期手术切除５９例。结果 流式细胞仪检测肿瘤细胞的凋记率,单纯手术组为１．７７％,行介入治疗的Ａ,Ｂ,Ｃ,Ｄ４个治疗组分别为６．１１％,８．７１     

术前化疗栓塞对不同大小肝细胞癌预后的影响

目的从整体、细胞和基因分子水平研究经导管动脉化疗栓塞(transcatheter arterial chemoembolization, TACE)对不同大小肝细胞癌(hepatocellular carcinoma, HCC)预后的影响.方法经手术病理证实的肝细胞癌110例,TACE后Ⅱ期手术切除53例(A组),单纯手术57例(B组),肿瘤直径≤8 cm者被分为A1组(18例)和B1组(30例);>8 cm者被分为A2组(35例)和B2组(27例).用流式细胞术检测凋亡率(apoptotic rate, AR)、S期细胞比率(S-phase fraction, SPF)和增殖指数(proliferative index, PI),用免疫组化检测各标本ras癌基因的表达蛋白p21、P-糖蛋白( P-glycoprotein, Pgp)、上皮型钙黏蛋白(epithelial cadherin, ECD)和nm23癌基因的表达蛋白二磷酸核苷激酶( nucleoside diphosphate kinase, ndpk).回顾分析各组这些标志物改变、肿瘤坏死、包膜形成情况,并统计肿瘤体积、转移率及累计生存率.结果肿瘤直径≤8 cm和>8 cm者,术前TACE均可引起肿瘤坏死、诱导凋亡、肿瘤包膜形成、体积缩小、转移潜能下降,1、2、3年累计生存率,A1组分别为94.4%、66.7%和44.4%,B1组分别为 90.0%、63.3%和40.0%(P>0.05);A2组分别为88.6%、60.0%和51.4%,B2组分别为59.3%、48.1% 和25.9%(P<0.05).结论术前TACE对所有肝细胞癌,尤其肿瘤直径>8 cm者安全有效.     

肝细胞癌TACE治疗进展

肝细胞癌（HCC）是世界上第五大常见肿瘤,我国肝癌的死亡率也位居前列。目前,手术是唯一有可能治愈HCC的方法。绝大多数病人来医院就诊时已经处于肝癌中晚期,对于此类病人,介入治疗是最主要的一种治疗方法。介入治疗又可分为血管性介入治疗和非血管性介入治疗。血管性介入治疗包括：经导管动脉化疗栓塞、肝动脉栓塞、肝动脉灌注化疗。经导管动脉化疗栓塞（TACE）是肝癌介入治疗的主要方法。主要对HCCTACE治疗的现状和进展进行综述。     

肝细胞癌TACE治疗进展

肝细胞癌(HCC)是世界上第五大常见肿瘤,我国肝癌的死亡率也位居前列。目前,手术是唯一有可能治愈HCC的方法。绝大多数病人来医院就诊时已经处于肝癌中晚期,对于此类病人,介入治疗是最主要的一种治疗方法。介入治疗又可分为血管性介入治疗和非血管性介入治疗。血管性介入治疗包括:经导管动脉化疗栓塞、肝动脉栓塞、肝动脉灌注化疗。经导管动脉化疗栓塞(TACE)是肝癌介入治疗的主要方法。主要对HCCTACE治疗的现状和进展进行综述。     

肝细胞癌经动脉化疗栓塞抵抗及后续治疗专家共识北大核心CSCD

经动脉化疗栓塞(transarterial chemoembolization,TACE)是目前治疗肝细胞癌(hepatocellular carcinoma,HCC)最常用方法之一。然而,重复进行无效的TACE治疗可能会加重肝功能损伤,影响患者预后。“TACE抵抗(TACE failure/refractoriness)”这一概念,即是在此背景下为避免进行重复无效的TACE治疗而提出的。但已有的多个“TACE抵抗”定义彼此间尚存在分歧,且均存在一定的局限性,对中国HCC人群是否适用也有待商榷。由中国医师协会介入医师分会(Chinese College of Interventionalists,CCI)成立的“TACE抵抗”协作组结合现有的循证医学证据及国内专家意见,于2021年提出了符合中国临床实践的“TACE抵抗”CCI定义及专家共识。“TACE抵抗”定义为:经过连续3次及以上规范化、精细化TACE治疗后,末次术后1~3个月内通过增强CT/MRI检查并基于mRECIST标准进行评估,若肝内靶病灶与首次TACE治疗前相比仍处于疾病进展状态,则为发生“TACE抵抗”,须及时终止再次TACE而转换为其他治疗。本共识的发布旨在使“TACE抵抗”概念更具科学性,从而更好地指导临床实践,进一步提高中国HCC患者TACE治疗受益率。     

术前经动脉化疗栓塞对肝细胞癌细胞凋亡的影响

目的 评价术前经导管动脉化疗栓塞(17ACE)对肝细胞癌(HCC)细胞凋亡的影响。资料与方法经手术病理证实的HCC136例，其中行1～5次TACE后Ⅱ期手术切除79例(TACE组)，按治疗方式不同分4组，A组：仅灌注化疗药物ll例，治疗1～4次；B组：化疗药 碘化油栓塞33例，治疗1～5次；C组：化疗药 碘化油 明胶海绵颗粒栓塞23例，治疗1—3次；D组：化疗药 碘化油、无水乙醇、明胶海绵颗粒栓塞12例，治疗1～3次。单纯手术57例(非TACE组)，用TUNEL(terminal deoxynucleotidyl transferase(TdT)-mediated dUTP-digoxigenin nick—end labeling)法检测凋亡细胞，用免疫组织化学检测各标本Bcl-2和Bax蛋白表达。结果 TACE组的A、B、C、D各组HCC细胞凋亡指数及Bax蛋白表达均显著高于非TACE组；而Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值TACE组的A、B、C、D各组均显著低于非TACE组。结论 术前TACE通过上调Bax蛋白表达，下调Bcl-2蛋白表达及Bcl-2和Bax蛋白表达比值使HCC细胞发生凋亡。     

肝动脉化疗栓塞术后残癌组织血管内皮生长因子表达的研究

目的研究肝细胞癌(HCC)经导管动脉化疗栓塞(TACE)后残癌组织血管内皮细胞生长因子(VEGF)的表达情况及其意义.资料与方法经病理证实的HCC63例,包括单纯手术切除42例(对照组),TACE术后行Ⅱ期手术切除21例(TACE组),TACE组患者手术前接受1～2次不等的TACE术治疗,均按统一规范标准给予化疗药物灌注 栓塞治疗,术中所用药物及栓塞材料为:5-Fu750～1500mg/次,顺铂80～120mg/次,吡柔比星20～40mg/次,羟基喜树碱20～30mg/次,40%超液化碘油20～30ml/次,明胶海绵1/5～1/3块/次.对手术切除标本进行免疫组织化学染色,其中TACE组取病灶边缘残存肿瘤部分,检测肿瘤组织VEGF的表达.结果 对照组VEGF阳性染色细胞数为138.26±65.24,TACE组残存肿瘤组织VEGF阳性染色细胞数为243.66±88.88,二者之间比较有显著性差异(t=5.34,P＜0.01),TACE显著上调了VEGF蛋白的表达.结论 TACE治疗后残癌组织存在丰富的肿瘤血供,残存肿瘤细胞VEGF表达明显升高,新生血管生成及VEGF的表达可能在栓塞后残癌组织血供重建中起到重要的作用.     

Necrosis and Apoptosis in Hepatocellular Carcinoma Following Low-Dose Versus High-Dose Preoperative Chemoembolization

Our purpose was to study necrosis and apoptosis of hepatocellular carcinoma (HCC) cells after preoperative transcatheter arterial chemoembolization (TACE) with use of low-dose and high-dose anticancer drugs in HCCs. Fifty-four patients with advanced but surgically resectable HCC were studied. Thirty-four patients who elected to undergo preoperative superselective TACE were randomized to low- and high-dose TACE. Patients in group A (n = 16) received low-dose anticancer drugs: 2 mg mitomycin C (MMC), 10 mg epirubicin (EPI), and 100 mg carboplatin (CBP). Patients in group B (n = 18) were given high doses of anticancer drugs (10 mg MMC, 40 mg EPI, and 300 mg CBP). Hepatic resection was subsequently performed. Group C comprised 20 patients who underwent resection without TACE. In all patients the necrosis rates and apoptosis index of tumor cells were evaluated by pathologic examinations and terminal deoxynucleotidyl transferase–mediated nick-end labeling assay. There was no significant difference between group A and group B in tumor response (p > 0.05) after TACE. Necrosis rates in groups A, B, and C were 88.4 ± 11.1%, 87.1 ± 12.5%, and 7.3 ± 3.5%, respectively. There was no significant difference between group A and group B (p > 0.05), while statistical difference was found between group A and group C (p < 0.001) and between group B and group C (p < 0.001). Apoptosis indexes in the three groups were 11.0 ± 4.0%, 10.7 ± 3.9%, and 5.6 ± 2.6%, respectively. Statistical difference exhibited between group A and group C (p < 0.001) and group B versus group C (p < 0.001). No significant difference was observed between group A and group B (p > 0.05). In conclusion, superselective TACE with low- and high-dose chemotherapeutic agents induced similar degrees of cellular apoptosis and necrosis.     

碘油栓塞后临床长期稳定肝癌病灶的MRI研究

目的:分析经导管动脉内化疗栓塞(TACE)治疗后临床长期稳定肝癌(HCC)的MRI表现,为临床可以长期随访或II期手术的肝癌患者提供指导。方法:42例HCC患者(86个病灶)TACE治疗后,经临床随访1年以上并证实为病灶稳定。28例54个病灶于治疗前行MRI检查,所有患者分别于治疗后3个月、12个月行MRI检查。常规行SET1WI、T2WI和3期动态增强扫描。回顾性分析各个时间点HCC的MRI表现及变化情况。结果:SE序列:T1WI上所有病灶在治疗前后不同时期信号改变无特异性。T2WI上治疗前52个病灶(52/54)为高信号,2个为等信号;治疗后3个月46个为等低信号,8个仍为高信号且信号强度高于治疗前;治疗后12个月所有病灶为等低信号。另14例32个病灶治疗后3个月T2WI上12个为高信号,20个为等低信号;治疗后12个月27个为等低信号,5个仍为高信号,但信号强度较前降低。动态增强扫描:治疗前54个(54/54)病灶增强早期均明显强化;所有病灶(86个)治疗后不同时期动态增强早期均未见强化,34个(34/86)病灶显示有完整和清楚的包膜。所有病灶均有不同程度的缩小,其中20个缩小>75%,44个缩小50%~75%,22个缩小25%~50%。结论:经TACE治疗后临床长期稳定的HCC病灶可靠的MRI表现为动态增强早期病灶无强化,包膜清楚、完整,体积缩小。T2WI呈等、低信号,高信号转变为等低信号或信号强度降低能提示病灶稳定。MRI平扫对病灶稳定性的判断需要密切随访和结合动态增强扫描。MRI能为适合临床长期随访或Ⅱ期切除的肝癌患者提供有价值的影像学信息。     

化疗栓塞对肝细胞癌PI、SPF、DI的影响

目的　研究不同化疗栓塞方法对不同组织学类型的肝细胞癌 (hepatocellularcarcinoma ,HCC)增殖指数 (proliferativeindex ,PI)、S期细胞比率 (S phasefraction ,SPF)、DNA指数 (DNAindex ,DI)的影响及PI、SPF、DI与HCC转移的关系 ,以便进一步研究化疗栓塞对HCC转移潜能的影响。材料与方法　 7种不同组织学类型的HCC共 98例 ,单纯手术 5 7例 ,4种化疗栓塞治疗后Ⅱ期手术切除 41例。采用流式细胞术 (flowcytometry ,FCM)检测各标本PI、SPF和DI ,并与转移情况对照。结果　PI和SPF与HCC转移潜能密切相关 (P <0 .0 1,P <0 .0 5 ) ,DI与转移关系不大 (P >0 .0 5 )。PI、SPF和DI存在组织学差异 ,Ⅲ级高于Ⅰ级 ,梁索型、索状腺样型、透明细胞型低于实体型和低 (未 )分化型。化疗栓塞使HCCPI、SPF下降 ,其中多材料联合化疗栓塞组 (C组和D组 )下降最明显 (P <0 .0 5 ) ;单材料化疗栓塞组 (B组 )PI上升最显著 (P <0 .0 5 ) ;重复 3～ 4次化疗栓塞PI、SPF下降显著 (P <0 .0 5 ,P <0 .0 1) ;化疗栓塞后1～ 2个月PI、SPF下降 ,2个月后增高。结论　HCC高转移性与高PI、SPF相关 ,化疗栓塞通过抑制HCC的PI、SPF来抑制其转移潜能 ,多次、多材料联合化疗栓塞且重复治疗间隔 <2个月抑制作用最强     

The Current Practice of Transarterial Chemoembolization for the Treatment of Hepatocellular Carcinoma

Despite remarkable advancement in the surveillance and treatment of hepatocellular carcinoma (HCC) and the availability of novel curative options, a great proportion of HCC patients are still not eligible for curative treatment due to an advanced tumor stage or poor hepatic functional reserve. Therefore, there is a continuing need for effective palliative treatments. Although practiced widely, it has only recently been demonstrated that the use of transarterial chemoembolization (TACE) provides a survival benefit based on randomized controlled studies. Hence, TACE has become standard treatment in selected patients. TACE combines the effect of targeted chemotherapy with the effect of ischemic necrosis induced by arterial embolization. Most of the TACE procedures have been based on iodized oil utilizing the microembolic and drug-carrying characteristic of iodized oil. Recently, there have been efforts to improve the delivery of chemotherapeutic agents to a tumor. In this review, the basic principles, technical issues and complications of TACE are reviewed and recent advancement in TACE technique and clinical applicability are briefed.     

肝动脉栓塞化疗术对肝细胞癌bcl-2、fas和bcl-xl表达的影响

目的　探讨经导管肝动脉栓塞化疗术 (TACE)对肝细胞癌 (HCC)细胞凋亡相关蛋白bcl 2、fas和bcl xl表达的影响 ,评价TACE对HCC的疗效。资料与方法　经病理证实的HCC 6 3例 ,包括单纯手术组 4 2例 ,TACE组 2 1例(为TACE治疗 2次后有手术机会而行切除者 ) ;采用免疫组织化学SP法检测标本bcl 2、fas和bcl xl的表达情况 ,将两组结果进行对照分析。结果　TACE组fas表达阳性率为 4 7.6 2 % (10 /2 1) ,单纯手术组fas表达阳性率为 2 1.4 3%(9/4 2 ) ,二者之间有显著性差异 (P <0 .0 5 ) ,TACE组明显高于单纯手术组 ;TACE组bcl xl表达阳性率为 2 3.81%(5 /2 1) ,单纯手术组阳性率为 5 4 .76 % (2 3/4 2 ) ,二者之间亦有显著性差异 (P <0 .0 5 ) ,TACE组明显低于单纯手术组 ;bcl 2的表达阳性率在单纯手术组和TACE组无显著性差异 (P >0 .0 5 )。结论　TACE治疗可以促进肝癌细胞fas表达增高 ,使bcl xl表达降低 ,从而在总体上增加肝癌细胞凋亡率 ,促使肿瘤缩小。关于TACE治疗对bcl 2的影响有待进一步研究     

ACI大鼠肝细胞癌模型的免疫化疗栓塞术研究

目的:评价生物反应调节剂(BRM)经肝动脉化疗栓塞术(TACE)治疗ACI大鼠肝细胞癌的疗效。方法:在30只雄性ACI大鼠肝包膜下植入Morris Hepatom 3924A肝癌瘤块(2 mm3),移植术后13天行MRI检查,测量肿瘤体积V1;第14天时,经腹部切开术及胃十二指肠动脉逆行插管而采取以下3种介入治疗方案:①A组,0.1 mg丝裂霉素、0.1 ml碘油、7.5μg TNFα和5×103IU IL-2(n=10);②B组,0.1 mg丝裂霉素、0.1 ml碘油、0.05 mg链球菌提取物(OK-432)和5×103IU IL-2(n=10);③C组(对照组),0.1 mg丝裂霉素、0.1 ml碘油(n=10);13天后再次行MRI检查以确定肿瘤体积V2变化。比较肝肿瘤体积生长率V2/V1。结果:肿瘤治疗前和治疗后体积分别为A组0.0377 cm3和0.2752 cm3;B组0.0344 cm3和0.2233 cm3;C组0.0380 cm3和0.3398 cm3。介入治疗后肿瘤体积与治疗前肿瘤体积之比(V2/V1)分别为A组7.31、B组6.53、C组9.14。与对照组相比,采取A组的治疗方案能抑制肝肿瘤体积的生长(P=0.042),采取B组的治疗方案能明显抑制肿瘤的生长(P=0.004)。结论:采取免疫化疗栓塞术能有效抑制ACI大鼠肝细胞癌的生长。     

Tumor Response to Transcatheter Arterial Chemoembolization in Recurrent Hepatocellular Carcinoma after Living Donor Liver Transplantation

Objective

To evaluate the tumor response and patient survival rate following transcatheter arterial chemoembolization (TACE) in recurrent hepatocellular carcinoma (r-HCC) after living donor liver transplantation (LDLT).

Materials and Methods

Twenty-eight patients with r-HCC underwent one or more cycles of TACE after LDLT (mean, 2.5 cycles). After a mixture of iodized oil and anti-cancer drugs was injected via the arteries feeding the tumors, these vessels were embolized with a gelatin sponge. Tumor response was determined by follow-up CT imaging on all patients four weeks after each TACE procedure. Patient survival was calculated using the Kaplan-Meier survival curve.

Results

After TACE, targeted tumor reduced in size by 25% or more in 19 of the 28 study patients (67.9%). However, intrahepatic recurrence or extrahepatic metastasis occurred in 21 of the 28 patients (75.0%) during the 3-month follow-up period and in 26 of the 28 patients (92.9%) during the 6-month period following TACE. Extrahepatic metastasis was noted in 18 of the 28 patients (64.3%). The 1-, 3- and 5-year survival rates following TACE were 47.9, 6.0 and 0%, respectively, with a mean survival of nine months in all patients. There were no significant complications related to TACE.

Conclusion

TACE produces an effective tumor response for targeted r-HCC after LDLT. However, the survival rate of patients with r-HCC after LDLT is poor due to extrahepatic metastasis and intrahepatic recurrence.     

CT Findings of Completely Regressed Hepatocellular Carcinoma with Main Portal Vein Tumor Thrombosis after Transcatheter Arterial Chemoembolization

Objective

The objective of this study was to determine the sequential CT findings of controlled hepatocellular carcinoma (HCC) with main portal vein (MPV) thrombosis with the use of transcatheter arterial chemoembolization and additional intra-arterial cisplatin infusion.

Materials and Methods

From January 2004 to September 2006, 138 patients with HCC invading MPV were referred to the angiography unit of our institution for chemoembolization and additional intra-arterial cisplatin infusion. Until August 2008, seven (5%) of 138 patients were followed-up and found not to have tumor recurrence. CT scans were retrospectively reviewed by two radiologists, focusing on the following parameters: the extent of portal vein thrombosis, the diameter of the affected portal vein, and enhancement of portal vein thrombosis.

Results

The extent of portal vein thrombosis at the initial presentation was variable: left portal vein (LPV) and MPV (n = 1), right portal vein (RPV) and MPV (n = 3), as well as RPV, LPV and MPV (n = 3). The extent and diameter of the affected portal vein decreased during follow-up examinations. In addition, the degree of enhancement for tumor thrombi and serum alpha-feto-protein levels decreased after the transcatheter arterial chemoembolization. Portal vein thrombosis was found to be completely resolved in one patient, whereas residual thrombus without viability was persistent in six patients.

Conclusion

If chemoembolization is effective in patients with HCC that invades the portal vein, the extent and enhancement of portal vein thrombosis is reduced, but residual thrombosis frequently persists for months or years, without evidence of a viable tumor.